Bristol-Myers Squibb and Five Prime Therapeutics, Inc. have entered into an exclusive worldwide license and collaboration agreement for the development and commercialization of Five Prime's colony stimulating factor 1 receptor (CSF1R) antibody program, including FPA008, which is in Phase I development for immunology and oncology indications. This agreement replaces the companies' existing clinical collaboration agreement to evaluate the safety, tolerability, and preliminary efficacy of combining Opdivo (nivolumab), Bristol-Myers Squibb's programmed-death 1 (PD-1) immune checkpoint inhibitor, with FPA008 in six tumor types.

Under the terms of the license and collaboration agreement, Bristol-Myers Squibb will make an upfront payment of $350 million to Five Prime. Bristol-Myers Squibb will be responsible for development and manufacturing of FPA008 for all indications, subject to Five Prime's option to conduct, at its own cost, certain future studies, including registrational studies to support approval of FPA008 in pigmented villonodular synovitis and FPA008 in combination with Five Prime's internal pipeline assets in immuno-oncology. Five Prime will continue to conduct the current Phase Ia/Ib trial evaluating the combination of Opdivo and FPA008 in six tumor settings, which was announced as part of the companies' initial clinical collaboration in November 2014, through to completion. Bristol-Myers Squibb will be responsible for global commercialization, and Five Prime will retain rights to a US co-promotion option. In addition to the upfront payment, Five Prime will be eligible to receive up to $1.05 billion in development and regulatory milestone payments per anti-CSF1R product for oncology indications (including combinations with Opdivo and any other agent), and up to $340 million in development and regulatory milestone payments per anti-CSF1R product for non-oncology indications, as well as double digit royalties, such royalties to be enhanced in the US in the event that Five Prime exercises its co-promotion option.

The effectiveness of the agreement is subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act.

FPA008 is an investigational antibody that inhibits CSF1R and has been shown in preclinical models to block the activation and survival of monocytes and macrophages. Early data have shown that inhibition of CSF1R in inflamed rheumatoid arthritis joints blocks the production of inflammatory cytokines by macrophages and inhibits osteoclasts, monocyte-lineage cells that can cause bone erosions and joint destruction. Inhibition of CSF1R in preclinical models of several cancers reduces the number of immunosuppressive tumor-associated macrophages (TAMs) in the tumor microenvironment, thereby facilitating an immune response against tumors. FPA008 is currently in Phase I clinical trials in several immunology and oncology indications.

Opdivo was first approved in Japan in July 2014 and currently has regulatory approval in more than 37 countries, including the United States, Japan, and in the European Union. In the US, Opdivo is indicated for patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. Opdivo is also approved for use in combination with Yervoy, for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma. Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials as a monotherapy or in combination with other therapies in which more than 8,000 patients have been enrolled worldwide.

Source: Bristol-Myers Squibb